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Landscape of stimulation-responsive chromatin across diverse human immune cells.
Calderon, Diego; Nguyen, Michelle L T; Mezger, Anja; Kathiria, Arwa; Müller, Fabian; Nguyen, Vinh; Lescano, Ninnia; Wu, Beijing; Trombetta, John; Ribado, Jessica V; Knowles, David A; Gao, Ziyue; Blaeschke, Franziska; Parent, Audrey V; Burt, Trevor D; Anderson, Mark S; Criswell, Lindsey A; Greenleaf, William J; Marson, Alexander; Pritchard, Jonathan K.
Afiliação
  • Calderon D; Program in Biomedical Informatics, Stanford University, Stanford, CA, USA.
  • Nguyen MLT; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Mezger A; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
  • Kathiria A; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Müller F; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Nguyen V; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Lescano N; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Wu B; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
  • Trombetta J; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
  • Ribado JV; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Knowles DA; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Gao Z; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Blaeschke F; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Parent AV; Department of Radiology, Stanford University, Stanford, CA, USA.
  • Burt TD; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Anderson MS; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
  • Criswell LA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Greenleaf WJ; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
  • Marson A; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
  • Pritchard JK; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
Nat Genet ; 51(10): 1494-1505, 2019 10.
Article em En | MEDLINE | ID: mdl-31570894
A hallmark of the immune system is the interplay among specialized cell types transitioning between resting and stimulated states. The gene regulatory landscape of this dynamic system has not been fully characterized in human cells. Here we collected assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing data under resting and stimulated conditions for up to 32 immune cell populations. Stimulation caused widespread chromatin remodeling, including response elements shared between stimulated B and T cells. Furthermore, several autoimmune traits showed significant heritability in stimulation-responsive elements from distinct cell types, highlighting the importance of these cell states in autoimmunity. Allele-specific read mapping identified variants that alter chromatin accessibility in particular conditions, allowing us to observe evidence of function for a candidate causal variant that is undetected by existing large-scale studies in resting cells. Our results provide a resource of chromatin dynamics and highlight the need to characterize the effects of genetic variation in stimulated cells.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos B / Cromatina / Células Matadoras Naturais / Linfócitos T / Regulação da Expressão Gênica / Elementos de Resposta Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos B / Cromatina / Células Matadoras Naturais / Linfócitos T / Regulação da Expressão Gênica / Elementos de Resposta Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos